Ruthenium catalysts and their use in the asymmetric hydrogenation of weakly coordinating substrates

ABSTRACT

A catalyst of Ru comprising bidentate phosphine ligands is described which is obtained by a process that comprises treating equimolar amounts of an appropriate Ru complex and a bidentate diphosphine ligand with an acid of the formula H-Anion, wherein the anion is a non-coordinating anion, said acid being used in a ratio of 1 molar equivalent per mole of Ru complex and the treatment being carried out in a non-coordinating or weakly coordinating medium, under an oxygen-free atmosphere. 
     Said catalyst is useful for the preparation of the preferred isomer of the Hedione®, having the configuration (+)-(1R)-cis, and of many other substrates comprising highly hindered carbon-carbon double bonds.

CROSS REFERENCE TO RELATED APPLICATION

This application is a continuation-in-part of application Ser. No.60/047,168 filed on May 20, 1997.

FIELD OF THE INVENTION AND PRIOR ART

The present invention relates to the field of asymmetric hydrogenationand, more particularly, to the use of novel Ru chiral catalysts for theasymmetric hydrogenation of substrates which, as a result of their weakdonor capability and of their hindered structures, have provedheretofore very difficult or impossible to hydrogenate.

A great number of chiral metal catalysts has been used in the past toasymmetrically hydrogenate a variety of substrates.

In the context of the present invention, we can cite in particular theefforts of two research groups which actively studied the synthesis ofRu chiral catalysts, obtained from the Ru(II) complex of formula[(COD)Ru(2-methylallyl)₂] (COD═cyclo-1,5-octadiene).

Thus, J.-P. Genet and his collaborators have published work related tocatalysts of formula [Ru(P*-P*)(2-methylallyl)₂], wherein P*−P*represents a diphosphine ligand of the type of those currently knownunder abbreviated designations such as DIOP, CHIRAPHOS, PROPHOS, BDPP,CBD, NORPHOS, DEGUPHOS, BPPM, BINAP, R-DuPHOS (R═methyl or ethyl),BIPHEMP or yet DIPAMP (see, for example, J.-P. Genet et al.,Tetrahedron: Asymmetry 1991, 2, 43). Such catalysts were obtained byheating the above-mentioned Ru(II) complex together with the appropriatechelating diphosphine, in a solvent such as hexane or toluene, such asto replace the cyclooctadiene with the chiral phosphine.

Upon subsequent work (see, for example, WO 91/02588; J.-P. Genet, AcrosOrganics Acta, 1994, 1, 1-8; J.-P. Genet et al., Tetrahedron: Asymmetry,1994, 5, 665-690), these authors described the transformation of suchcatalysts via protonation by means of aqueous acids such as HBr, HCl, HFor HBF₄, in strongly coordinating solvents, capable of playing a role instabilizing the coordination structure around the metal, whichstructure, according to the same authors, is of the hexacoordinate type.This kind of catalysts, which can be prepared in situ, proved to beuseful for the asymmetric hydrogenation, in protic or stronglyelectron-donating solvents (methanol, ethanol or their mixtures withother solvents), of substrates comprising carbonyl groups and acyclicethylenic bonds.

Other studies (see, for example, F. Heiser et al., Tetrahedron:Asymmetry, 1991, 2, 51-62; EP 643 052; EP 398 132; EP 570 674) haveresulted in reports of the use of catalysts prepared in situ forhydrogenating a variety of substrates, starting from the same rutheniumcomplex, but following a process according to which a mixture of saidcomplex and an appropriate diphosphine ligand is treated with namelyCF₃COOH, once again in an electron-donor solvent able to stabilize thecoordinating structure of the metal.

These catalysts, and others obtained according to similar processesdescribed in the cited references, reveal themselves very efficient inthe asymmetric hydrogenation of various substrates, often goodelectron-donor substrates capable of coordinating the Ru, and aretypically used with protic solvents, or mixtures of protic and aproticsolvents. However, they proved to be inefficient when used, under theprior art conditions, for the hydrogenation of substrates possessingheavily hindered ethylenic bonds, for example tetrasubstituted doublebonds, in particular when the latter are part of ring systems.

In published International patent application N° WO 97/18894, filed onNov. 20, 1996, we describe new Ru catalysts and teach their successfuluse for asymmetrically hydrogenating this type of particularly hinderedsubstrates. More particularly, there is described the hydrogenation ofcyclopentenone derivatives of formula (II)

wherein R¹ represents a linear or branched C₁ to C₄ alkyl radical and R²represents a saturated or unsaturated, linear or branched, C₁ to C₈hydrocarbon radical, the hydrogenation of which had proved impossibleuntil our discovery of novel catalysts obtained by an original process.

The catalysts described in the above-mentioned patent application wereobtained by a method which comprised treating equimolar amounts of anappropriate Ru complex, for example [(COD)Ru(2-methylallyl)₂] and achelating diphosphine with an acid of formula HX, wherein X is anon-coordinating anion, said acid being used in a ratio not exceeding 2molar equivalents per mole of the Ru complex and the treatment beingcarried out in a non-coordinating or weakly coordinating medium, underan inert atmosphere.

Such catalysts were able to successfully hydrogenate substrates (formulaII), amongst others, to provide their corresponding saturated homologuesin strictly cis-configuration and with an enantiomeric excess of atleast 60% in the (+)-1R-isomer. Such catalysts, and their use inasymmetric hydrogenation reactions, provided a breakthrough ofoutstanding importance for the single-step conversion of unsaturatedsubstrates which had previously proved impossible to hydrogenate, intotheir saturated homologues. Moreover, their use in the conversion ofsubstrates (formula II) proved particularly valuable in the case ofmethyl 3-oxo-2-pentyl-1-cyclopentene-1-acetate, the asymmetrichydrogenation of which provided, in a single step, the preferredoptically active isomer of methyl dihydrojasmonate or Hedione® (origin:Firmenich S A, Geneva, Switzerland), a well-known and widely usedperfume ingredient.

In fact, amongst the four possible Hedione® stereoisomers, methyl(+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentaneacetate is known to develop attheir best the odor characters, and namely the jasmine note, for whichHedione® is notorious, while the strength of this isomer's odor is alsosuperior to that of the other isomers by several orders of magnitude.Therefore, the production of methyl(+)-(1R)-cis-3-oxo-2-pentyl-1-cyclopentaneacetate in an optically purestate, or of isomer mixtures which contain essentially this isomer, isof capital importance in the fragrance industry.

DESCRIPTION OF THE INVENTION

One object of the present invention is a ruthenium catalyst obtainableby a process which comprises putting into contact an appropriate Rucomplex, a chelating diphosphine and an acid comprising anon-coordinating anion, said Ru complex and chelating diphosphine beingpresent in equimolar amounts, the contact occurring in anon-coordinating or weakly coordinating medium and under an oxygen-freeatmosphere, wherein the acid comprising the non-coordinating anion isused in an amount of about 1 molar equivalent per mole of the Rucomplex.

Reference to “about 1 molar equivalent of acid per mole of Ru complex”signifies here a molar ratio between these two components which does notsignificantly differ from 1, and is preferably comprised within a rangeof between 0.95 and 1.10, more preferably from 1.0 to 1.10.

The above-mentioned catalysts of the invention provide surprisingly goodresults when used in the hydrogenation of substrates (formula II) inparticular, but can also be conveniently used for the hydrogenation ofsubstrates of general formula (III)

as defined in claim 12. Preferred embodiments of the hydrogenationprocess of the invention relate to the hydrogenation of substrates(formula III) having a carbon-carbon double bond in one of the positionsindicated by the dotted lines which is at least trisubstituted, i.e. notmore than one amongst the R², R³ and R⁴ groups represents hydrogen.

It will be apparent to the person skilled in the art from the disclosurewhich follows that the catalysts of the invention can also besuccessfully used in the hydrogenation of ethylenic bonds lesssterically hindered than those of preferred substrates (formula III)described above. However, they are most advantageously used in theone-step conversion of the preferred substrates (III) defined above intotheir saturated homologues, as is apparent hereafter, particularly thosewherein the double bond is tetrasubstituted.

We have in fact ascertained that the catalysts of the invention can besuccessfully and generally used in asymmetric hydrogenations and areable to readily hydrogenate di-, tri- and tetrasubstituted double bonds,isolated occurred or in α,β- or β,γ-position to an ester function, inα,β-position to a ketone or aldehyde function and even in β,γ-positionto an alcohol function, the ester and ketone groups being totallyunaffected by the hydrogenation.

The catalysts of the invention comprise, or consist essentially of, thereaction product of the appropriate Ru complex, the chelatingdiphosphine and the acid comprising the non-coordinating anion, thereaction occurring in a non-coordinating or weakly coordinating medium.

By an “appropriate Ru complex” it is meant here any of the Ru complexescurrently known and used in the preparation of ruthenium catalysts,amongst which can be cited for example those wherein the metal issurrounded by dienyl and alkyl type ligands, such that the metal isσ-bonded to two of said ligands, which ligands further possess at leastone bond π-bond to the metal, two other coordination positions beingπ-bonded to the same said two ligands or to a distinct ligand.

Several ruthenium compounds are known from the prior art which compriseligands fulfilling the above-mentioned conditions and which areconvenient as precursors of the catalysts of the present invention.

One can cite more particularly, as appropriate Ru complexes, thecompounds of the [(diene)Ru(allyl)₂] type, wherein “diene” stands forexample for COD (cycloocta-1,5-diene) or NBD (norbornadiene), or yethepta-1,4-diene, and “allyl” represents an allyl or 2-methylallylradical (see, for instance, J.-P. Genet et al., cited references; M. O.Albers et al., Inorganic Synth., 1989, 26, 249; R. R. Schrock et al., J.Chem. Soc. Dalton Trans., 1974, 951). Other appropriate ruthenium(II)complexes include the compounds of the [bis(pentadienyl)Ru] type,wherein “pentadienyl” stands for a pentadienyl, 2,4-dimethylpentadienyl,2,3,4-trimethylpentadienyl, 2,4-di(tert-butyl)-pentadienyl or yet2,4-dimethyl-1-oxapentadienyl radical (see, for example, R. D. Ernst etal., J. Organometallic Chem., 1991, 402, 17; L. Stahl et al.,Organometallic 1983, 2, 1229; T. Schmidt et al., J. Chem. Soc. Chem.Commun., 1991, 1427; T. D. Newbound et al., Organometallics, 1990, 9,2962).

Yet other appropriate Ru complexes include [Ru(COD)(COT)], wherein COTstands for cycloocta-1,3,5-triene, [bis(2,4-cyclooctadienyl)Ru] and[bis(2,4-cycloheptadienyl)Ru] (see, for example, P. Pertici et al., J.Chem. Soc. Dalton Trans., 1980, 1961; Inorganic Synthesis 1983, 22, 176)and [Ru(NBD)(CHT)] wherein NBD is norbornadiene and CHT stands forcyclohepta-1,3,5-triene (see for example, H. Nagashima et al., J.Organometallic Chem. 1983, 258, C15).

Following a preferred embodiment of the catalysts of the invention,there is used as the Ru precursor, the compound of formula: [(COD)Ru(2-methylallyl)₂], bis(2,4-dimethylpentadienyl)ruthenium (e.g. L. Stahlet al. or T. D. Newbound et al., references cited),bis(2,4-dimethyl-1-oxapentadienyl) ruthenium complexes (e.g. T. Schmidtet al., reference cited) or yet [Ru(COD)(COT)] (P. Pertici et al., ref.cited). [(COD)Ru(2-methylallyl)₂], the preparation of which was firstreported by J. Powell et al., in J. Chem. Soc., (A), 1968, 159 (see alsoM. O. Albers et al., Inorganic Synthesis 1989, 26, 249, and[Ru(COD)(COT)] proved quite convenient from a practical point of view.

Amongst the chelating diphosphines which can be used as ligands in thecatalysts of the invention, there can be cited as preferred embodimentsthose selected amongst the known chiral diphosphine or bis(phosphine)ligands which make it possible to obtain catalytic species convenientfor homogeneous asymmetric hydrogenations. More particularly, suchchiral diphosphines include those known under the abbreviations ofMe-DuPHOS, Et-DuPHOS, BINAP, TolBINAP, SKEWPHOS, DIPAMP and CHIRAPHOS,the structures of which are represented hereafter for one of theenantiomers in particular, and wherein Ph stands for a phenyl group:

Other chiral bidentate phosphines which can be used in the chiralcatalysts of the invention include for instance those known under thename of NORPHOS, or yet the analogues of the DuPHOS type ligands,so-called “BPE”, the structures of which are represented hereafter forone of the enantiomers.

All such ligands are either commercially available or can be prepared bymethods previously reported in the literature.

Other particularly useful ligands for the preparation of the catalystsof the invention are the chiral diphosphines described for example inEuropean patent applications nos. 564 406, 612 758 and 646 590, whichdisclose a large number of ligands appropriate for the catalystsaccording to the present invention. The contents of these documents,inasmuch as they relate to the definition and preparation or saidchelating diphosphines, are hereby included by reference.

Amongst the chelating diphosphines described in EP 564 406, EP 612 758and 646 590, it is preferred to use those obeying the general formula(L′8)

wherein P is a phosphorus atom and R and R′ are, independently from eachother, a C₁ to C₄ alkyl group, linear or branched, a cyclohexyl group, aphenyl group or a phenyl group substituted by 1 to 3 alkyl groups having1 to 4 carbons, the latter alkyl groups possibly being partially ortotally fluorinated.

Even more preferred ligands of this type are those of formula

and, more particularly, that known under the designation of(R)—(S)-JOSIPHOS (R=cyclohexyl, R′=phenyl) or (−)-JOSIPHOS, or yet itsderivatives such as (R)—(S)—CF₃-JOSIPHOS.

Moreover, we also observed that the catalysts of the invention provedadvantageous for the hydrogenation of many substrates, in particularthose of formula (II), with a cis-stereoselectivity close to 100%, whenthey comprised in their structure both chiral and achiral chelatingdiphosphines. Thus, useful achiral ligands include for example theachiral or racemic ferrocenyl diphosphines represented hereafter:

Other bidentate phosphines useful as ligands are represented below:

In the context of the invention, there can yet be cited the opticallyactive diphosphines of formula (L14)

as well as the corresponding racemic mixtures of isomers, reported inInternational patent application WO 96/20202. The contents of the latterrelated to the preparation of such ligands are hereby included byreference.

In a general manner, there can be used as ligands in the catalysts ofthe invention any chelating diphosphines comprising substituent groupscapable of rendering the diphosphine sufficiently electron-rich to allowit to stabilize the metal, without however depriving said metal of itsability to coordinate the substrate to be hydrogenated and moreparticularly substrates of formula (II) and (III) mentioned above, theasymmetric hydrogenation of which had proved heretofore notoriouslydifficult, if not impossible.

It has also been observed that the diphosphines having a certain numberof alkyl or cycloalkyl type substituents revealed themselvesparticularly useful for the aim of the invention and provided catalystswhich were very active and efficient for the hydrogenation of substratesof formula (II) and (III).

It is apparent from the above that the preferred ligands for preparingthe catalysts of the invention are diphosphine ligands in which the twophosphorous atoms are bridged by groups of the alkyl, 1,2-benzenyl,bis(naphthalenyl) or yet 1,1′-ferrocenyl type, optionally substituted,said phosphorous atoms further carrying two other substituents, whichcan be identical or different and formed of alkyl, aryl or alkylarylradicals, or yet alicyclic radicals.

However, it is impossible to exhaustively illustrate here all theligands which can be used in the catalysts of the invention and manyother chelating diphosphines, not specifically cited above, or notfalling under the above definitions, prove useful for the aim of thelatter. The examples given illustrate preferred embodiments which arenot to be interpreted as restricting the scope of the invention,inasmuch as the person skilled in the art is well able, withoutparticular effort and using her general knowledge to select such ligandsso as to achieve the aim described. To this effect, the skilled personcan also find inspiration in the many prior art references, namely thosecited in this description, to select many such ligands which, when usedaccording to the invention here-described, make it possible to obtaincatalysts able to achieve the same effect, i.e. hydrogenate substratesof formula (II) and (III) with essentially cis-stereo-selectivity (90%or more) for (formula II), and providing, where applicable, an excess ofat least 60% in one of the cis-enantiomers.

The catalysts of the invention which comprise diphosphine ligands of theDuPHOS, BINAP, TolBINAP, SKEWPHOS or JOSIPHOS type are particularlyadvantageous as catalysts for the asymmetric hydrogenation of thesubstrates of formula (II) and (III).

Amongst the latter catalysts, those which comprise ligands of theSKEWPHOS, JOSIPHOS or Me-DuPHOS type, and preferably of the two lattertypes, showed themselves capable of particularly advantageousperformances and are therefore preferred according to the invention.(R,R)-(−)-Me-DuPHOS, or (−)-1,2-bis(2,5-dimethyl-phospholano)benzene,and (R)—(S)-JOSIPHOS or (R)—(S)—CF₃-JOSIPHOS, made it possible to obtainchoice catalysts according to the invention.

The ligands having formula L1 to L14 represented below are eithercommercially available compounds or they can be prepared according toprocesses analogous to previously described methods.

For example, the ligands of the DuPHOS, SKEWPHOS, BINAP, CHIRAPHOS,DIPAMP and NORPHOS type are mostly commercial products and, in anyevent, they can be obtained via processes described in the literature,namely in reference works such as the books of R. Noyori, AsymmetricCatalysis in Organic Synthesis, John Wiley & Sons, N.Y. (1994), Chap. IIand J. Ojima, Catalytic Asymmetric Synthesis, VCH Publishers, N.Y.(1994), Chap. I, and the original references there-cited wherein suchligands were first reported.

The ligands of formula (L7) can be prepared as described for example inU.S. Pat. No. 5,171,892.

The ligands of formula (L8) and (L′8) can be prepared as described inthe references already cited (see also A. Togni et al., J. Amer. Chem.Soc. 1994, 116, 4062) and some of them are commercially available(R=cyclohexyl, R′=phenyl for example; origin: STREM Chemicals, Inc.).

The ferrocenyl ligands of formula (L9), (L10) or (L11), when notavailable commercially, can be prepared by methods analogous to thosereported in the literature (see, for example, I. R. Butter et al.,Synth. React. Inorg. Met.—Org. Chem., 1985, 15, 109; M. D. Rausch etal., J. Organometallic Chem., 1967, 10, 127; R. A. Brown et al.,Polyhedron 1992, 20, 2611; G. Herberich et al., Chem. Ber., 1995, 128,689) starting from ferrocene and according to the following reactionschemes:

The (L12) and (L13) ligands are quite common and many arecommercialized. Amongst the (L13) ligands, those wherein n=0 can beprepared by a variety of known methods (see, for example, R. Appel etal., Chem. Ber., 1975, 108, 1783 and references cited therein; M.Baudler et al., Chem. Ber. 1972, 105, 3844; K. Issleib et al., Journalfür Praktische Chemie, 1969, 311, 463).

The non-coordinating anion to be used in the catalysts of the inventioncan be a conjugate base of a variety of strong acids and includes forexample the anions selected from the group consisting of BF₄ ⁻, PF₆ ⁻,SbF₆ ⁻, AsF₆ ⁻ and B[3,5-(CF₃)₂C₆H₄]₄ ⁻. Thus, suitable acids thatcontain this conjugate anion include, amongst others, those of formulaRBF₄, RPF₆, RSbF₆, RAsF₆, and RB[3,5-(CF₃)₂C₆H₄]₄ wherein R representshydrogen or a (C₆H₅)₃C group.

According to a preferred embodiment of the invention, thenon-coordinating anion is a conjugate base of an acid of formulaH-anion, wherein the anion is selected amongst the anions BF₄ ⁻, PF₆ ⁻,SbF₆ ⁻, AsF₆ ⁻; or yet HB[3,5-CF₃)₂C₆H₄]₄ ⁻. Such acids are typicallyused in the form of the corresponding etherates (for example HBF₄.R₂O,R═CH₃ or C₂H₅) or of any other onium type salt (phosphonium forexample). These etherates are commercial products, or they can beprepared from the corresponding silver salts, by reacting with HCl. Inthe latter case, the silver salt, for example AgBF₄, AgPF₆, AgSbF₆ orAgAsF₆ will be typically reacted with HCl, in a solvent containing adialkylether, for example a mixture of dicholormethane and diethylether.As the silver chloride precipitates, it provides the etherate solutionof the acid, which can then be used according to the invention in thereaction with the ruthenium complex and the phosphine ligand.

Amongst the above-mentioned H-Anion acids, wherein the anion representsthe non-coordinating anion, tetrafluoroboric acid is preferred andtypically used in the form of its etherate, as commercially available inglass or plastic vials. If necessary, this product is titrated to ensurethat the concentration of acid is about 1 molar equivalent of the molaramount of Ru complex.

The reaction according to which the catalyst of the invention can beobtained occurs in a non-coordinating or weakly coordinating medium andunder an oxygen-free atmosphere. By an “oxygen-free atmosphere” it ismeant here an atmosphere whose oxygen content is lower than 200 ppm, andpreferably not above 5 to 10 ppm.

By the “non-coordinating or weakly coordinating medium” it is typicallymeant here a non-coordinating or weakly coordinating solvent. Examplesof suitable solvents include esters, ketones, aliphatic, acyclic orcyclic hydrocarbons, chlorinated hydrocarbons and ethers, as long asthey have no capability to strongly coordinate the ruthenium. Specificexamples include dichloromethane, dichloroethane, ethyl pivalate, methylacetate, ethyl acetate, isopropyl acetate, acetone, 2-butanone,3-pentanone, hexane, heptane, cyclohexane, cycloheptane and methyltert-butyl ether.

According to a preferred embodiment, dichloromethane or a mixture of itwith other, non-coordinating or weakly coordinating solvents, inparticular those mentioned above, is used.

It should be noted that the use of the strongly coordinating or proticsolvents current in the art for the preparation of Ru catalysts,provided species which were inactive or inadequate for the hydrogenationof the substrates of formula (II) or (III) previously mentioned.

The non-coordinating or weakly coordinating medium may also consist of amixture of a solvent such as described above with a substrate of formula(II) or (III), or even essentially of just said substrate of formula(II) or (III).

Thus, according to an embodiment of the invention there is provided acatalyst obtainable in the presence of an organic non-coordinating orweakly coordinating solvent and/or of a substrate of formula

having a double bond in one of the positions indicated by the dottedlines and wherein

a) n=0 and Z represents hydrogen, a C₁ to C₄ linear or branched alkylradical or an OR¹ group, R¹ standing for a linear or branched loweralkyl radical; or

b) n=1, X represents a CH₂ group and Z stands for an OR¹ group whereinR¹ has the meaning cited in a); or

c) n=1, X represents an oxygen atom and Z represents a C₁ to C₄ linearor branched alkyl radical, or X represents a NR⁵ group, R⁵ standing fora lower alkyl radical, and Z stands for a linear or branched C₁ to C₄alkyl radical and wherein

R² represents hydrogen or a saturated or unsaturated, linear or branchedC₁ to C₈ radical derived from a hydrocarbon;

R³ and R⁴ are taken separately and each represents hydrogen or asaturated or unsaturated, linear or branched C₁ to C₈ radical derivedfrom a hydrocarbon, or are taken together to form a five-membered orsix-membered ring which also contains the carbon atoms of the ethylenicbond.

Preferred substrates of the invention are compounds of formula (III)wherein not more than one of the R², R³ and R⁴ symbols representshydrogen.

By a lower alkyl radical it is meant here a C₁ to C₄, linear or branchedalkyl radical.

When the catalyst of the invention is obtained in the presence of thesubstrate, preferred embodiments of said catalyst include the presenceof substrates formed of compounds of formula (II)

wherein R¹ is a linear or branched alkyl radical from C₁ to C₄ and R² isa saturated or unsaturated, linear or branched, C₁ to C₈ hydrocarbonradical, or of formula

having a double bond in one of the positions indicated by the dottedlines and wherein:

a) n=0 and Z represents an OR¹ group, R¹ standing for a C₁ to C₄ linearor branched alkyl radical; or

b) n=1, and Z represents a C₁ to C₄ linear or branched alkyl radical;and wherein R² is a saturated or unsaturated, linear or branched, C₁ toC₈ hydrocarbon rest and R⁶, R⁷ and R⁸ represent each hydrogen or a loweralkyl radical of C₁ to C₄.

In this context, particularly useful catalysts are those wherein thesubstrate present in the reaction medium is a compound of formula (IV)in which n=0 and Z represents a OR¹ group wherein R¹ represents a methylor ethyl group, R² represents a methyl radical and R⁶, R⁷ and R⁸ areidentical or different and represent each hydrogen or a methyl group.

More preferred substrates are methyl3-oxo-2-pentyl-1-cyclopentene-1-acetate and methyl2,6,6-trimethyl-2-cyclohexene-1-carboxylate, which, as will becomeapparent shortly, make it possible to obtain preferred isomers of usefulperfume ingredients, amongst which Hedione®.

As previously mentioned, the medium in which the reaction takes placecan also be a mixture of one of the substrates mentioned above and anon-coordinating or weakly coordinating solvent, in which case thelatter will be preferably chosen amongst the solvents already citedabove, and more preferably as a solvent comprising dichloromethane.

The catalysts of the invention described above are extremely activespecies which have been found to improve upon those described in the WO97/18894 patent application. In fact, although the catalysts describedin the above document are quite appropriate for the hydrogenation of thesame type of ethylenic bonds and substrates as are here contemplated, wehave now unexpectedly discovered that complete conversion of thesesubstrates can now be obtained, by means of the presently claimedcatalysts, in even shorter reaction times, while using lower amounts ofcatalyst.

Amongst the catalysts of the invention described above, particularlyeffective species for the asymmetric hydrogenation of methyl3-oxo-2-pentyl-1-cyclopentene-1-acetate were those wherein the Rucomplex is [(COD)Ru(2-methylallyl)₂] and the anion BF₄ ⁻ derived fromHBF₄.etherate, and wherein (R,R)-(−)-Me-DuPHOS or (R)—(S)-JOSIPHOS wasused in a medium comprising dichloromethane, in both cases preferably inthe presence of the substrate mentioned here-above.

The invention further realizes a process for the preparation of aruthenium catalyst, characterized in that an appropriate Ru complex anda chelating diphosphine present in equimolar amounts, and an acidcomprising a non-coordinating anion, are reacted under an oxygen-freeatmosphere and in a non-coordinating or weakly coordinating medium,wherein the acid comprising the non-coordinating anion is used in anamount of about 1 molar equivalent per mole of the Ru complex.

The nature of the parameters of this process, i.e. the Ru complex, thechelating diphosphine, the non-coordinating anion and the reactionmedium, have been described in detail above.

According to the invention, the preparation of the catalyst can becarried out at room temperature or at a lower temperature. Highertemperatures may also be used, and can be chosen such as not toinfluence the catalyst's properties and its efficiency in thehydrogenation of the substrates. Nevertheless, the application of roomtemperature proves to be advantageous from a practical point of view.

As mentioned before, the catalyst is prepared under inert, oxygen-freeatmosphere, typically under argon or nitrogen.

Preferred embodiments of this process correspond to the use of thepreferred parameters already described above with regard to thecatalysts, e.g. the use of optically active diphosphines, preferredanions and so on.

In particular, the preparation of the catalyst in a medium consisting ofa non-coordinating or weakly coordinating solvent and a small amount ofsubstrate, in particular substrates of formula (II) or (IV), turns outto be a very advantageous embodiment of the process of the invention.

The catalysts according to the present invention which have beenprepared like this are obtained as solutions, in the solvent and thesubstrate, of the product which is the result of the reaction of the Rucomplex with the diphosphine ligand and the acid from which the anion isderived. These catalytic solutions may be used as such for theasymmetric hydrogenation of the substrates, namely compounds of formula(II) and (IV). They can be kept under an oxygen-free atmosphere and willstay active for several days.

Catalytic solutions according to the present invention are thusobtained, having a variable concentration in the catalyst of theinvention, for example of the order of 0.04 to 0.07 M (0.04 to 0.07mmoles of catalyst/ml of catalytic solution), and more preferably of theorder of 0.055 M, which proved to be very advantageous for thehydrogenation of substrates formula (II) and (IV) in particular.

Preferred pre-catalysts of the invention are those of formula

[Ru(P*−P*)(H)(triene)]⁺Anion⁻  (V)

wherein P*−P* represents a chelating bis(phosphine)ligand, possiblychiral, X represents a non-coordinating anion and “triene” stands forcyclohepta-1,3,5-triene, cycloocta-1,3,5-triene or a similar species.These most preferred compounds require the presence of at least one CODmolecule in the precursor Ru complex. According to a preferredembodiment of this catalyst, the diphosphine is (R,R)-(−)-Me-DuPHOS or(R)—(S)-JOSIPHOS and the anion is BF₄ ⁻.

Other embodiments of this catalyst are apparent from the text above, thediphosphine ligand and the anion being varied at will, having themeaning previously defined and being specifically cited above withregard to particular examples of the catalysts of the invention.

The preparation of preferred embodiments of the catalysts of formula (V)are described in detail further on.

The ruthenium catalysts of the invention are useful for thehydrogenation, optionally asymmetric, of carbon-carbon double bonds ingeneral and more particularly highly sterically hindered ones.

Their activity with regard to the hydrogenation of the substrates offormulae (II), (III) and (IV) in particular is excellent, unlike what isthe case of the prior art ruthenium catalysts. They enable thepreparation of the saturated compounds corresponding to substrates offormula (II) and (IV) with a cis-stereoselectivity above 95% and, inmost cases of the order of 98% or more. When chiral chelatingbis(phosphines) are present in the structure of the catalysts of theinvention, the asymmetric hydrogenation of the above-mentionedsubstrates provides enantiomers with at least 60% e.e., and in manycases above 85% ee.

According to preferred embodiments of the invention, there are thus alsoprovided processes for the preparation of compounds resulting from thehydrogenation of compounds of formula (II) and (IV).

Therefore, the invention also relates to a process for the preparationof a compound of formula

wherein R¹ is a linear of branched C₁ to C₄ alkyl radical and R² is asaturated or unsaturated, linear or branched C₁ to C₈ hydrocarbon rest,essentially in the form of an isomer of cis-configuration, characterizedin that a substrate of formula

in which R¹ and R² have the meaning indicated above, is hydrogenated inthe presence of a Ru catalyst as previously described and at a hydrogenpressure comprised between atmospheric pressure and 500 bar (5×10⁷ Pa).

Another object of the invention is a process for the preparation of acompound of formula

wherein the dotted lines and the symbols n, Z, R², R⁶, R⁷ and R⁸ aredefined as in formula (IV), essentially in the form of an isomer ofcis-configuration, characterized in that a substrate of formula (IV) asdefined above is hydrogenated in the presence of a ruthenium catalystaccording to the invention and at a hydrogen pressure comprised betweenatmospheric pressure and 500 bar.

Preferred embodiments of these two processes resort to the use ofcatalysts which comprise appropriate chiral chelating diphosphines, suchas to provide the compound of formula (I) or (VI) essentially in theform of an optically active isomer of cis-configuration.

As is current in the art, the substrate is preferably used in a purestate and free of oxygen.

The hydrogenation reaction can be carried out in a non-coordinating orweakly coordinating solvent, the latter being defined as alreadydescribed above. Specific examples thus include dichloromethane,dichloroethane, ethyl pivalate, methyl acetate, ethyl acetate, isopropylacetate, acetone, 2-butanone, 3-pentanone, hexane, heptane, cyclohexane,cycloheptane and methyl tert-butyl ether, and their mixtures. The use ofa solvent comprising dichloromethane is preferred.

Alternatively, the hydrogenation medium in which the reaction takesplace may consist essentially of the substrate, or be highlyconcentrated in the latter.

According to a preferred embodiment of the hydrogenation process of theinvention, the catalyst is generated in situ before the hydrogenation ofthe substrate, or in the presence of a small amount of the latter.

All the racemic or achiral ligands previously cited can be used togenerate catalysts which make it possible to prepare the compounds offormula (I) or (VI) essentially in the form of the cis-configurationisomer, whereas the optically active chelating diphosphines provide thedesired optically active cis form of the cited compounds of formula (I)or (VI).

Of course, racemic ligands can be subjected to separation, for exampleby means of chiral columns, to provide the corresponding enantiomers.

Following a particularly preferred embodiment of the hydrogenationprocess according to the present invention, methyl3-oxo-2-pentyl-1-cyclopentene-1-acetate is used as the substrate, inorder to obtain Hedione® in the form of the preferred cis- and(+)-cis-configuration isomers.

The catalysts according to the present invention which start from the[(COD)Ru(2-methylallyl)₂] precursor and have ligands of the DuPHOS type,and in particular Me-DuPHOS, have proved to be particularly useful forthe hydrogenation of this substrate, carried out in a solvent ofdichloromethane.

Other preferred conditions for the hydrogenation of this substrateinclude the use of a catalyst comprising [(COD)Ru(2-methylallyl)₂] and(R)—(S)-JOSIPHOS as the ligand, in a hydrogenation medium comprising ahydrocarbon such as hexane, heptane or their saturated cyclic analogues,and more preferably methyl tert-butyl ether.

This latter preferred embodiment of the hydrogenation process of theinvention makes it possible to obtain (+)-cis-Hedione® with anenantiomeric excess of 80% or more. Still another preferred embodimentresorts to the use of [Ru(COD)(COT)] and (R)—(S)-JOSIPHOS.

The hydrogenation can be carried out at pressures from about atmosphericpressure to 500 bar (5×10⁷ Pa). Pressure values comprised between 20,and more preferably 50 to 200 bar or even higher are quite convenient.

The reaction may take place at temperatures of up to 50 to 60° C., oreven 100° C. Preferably, one will work at room temperature or even alower temperature. It has been found for example that temperatures downto −10° C., or even lower, made it possible to obtain good results.

The molar concentrations in which these catalysts may be typically usedcan go up to 4 molar %, relative to the substrate, but preferredembodiments of the hydrogenation process of the invention comprise usingthe catalyst in a molar concentration of about 0.01 to 1%, morepreferably between 0.01 and 0.5 molar %. Excellent results could besystematically obtained with concentrations of 0.02 to 0.1%, moreparticularly 0.025 to 0.05 molar %, relative to the substrate.

Moreover, it has also been found that it is advisable to use solutionsin which the substrate is concentrated, and the best results have beenobtained when the concentration of the substrate in the hydrogenationmedium was from about 0.4 to 1.5 molar with respect to the volume ofthis medium.

To hydrogenate the reaction mixture, the latter is pressurized underhydrogen in a conventional manner and as is described in the examplesbelow. With the catalysts of the invention, used in concentrations ofthe order of 0.05 molar % relative to the substrate complete conversionof the latter could be obtained in less than 24 h, and in the best casesin 6 hours or less.

The invention will now be described in greater detail by way of thefollowing examples, wherein the temperatures are indicated in degreesCelsius and the abbreviations have the usual meaning in the art.

These examples illustrate particular and best embodiments of theinvention, many variations of which can be readily construed from thedescription above. Namely, in the many examples of catalysts taught inthe WO 97/18894 application, which resulted from the variouscombinations of the preparation parameters also described in detail inthe preceding pages of the instant disclosure, the use of about 1 molarequivalent of acid comprising a non-coordinating anion per mole of Rucomplex, as instantly taught, provided enhanced novel catalysts. Thecontents of this WO 97/18894 application is therefore hereby included byreference, to the extent that it provides specific examples of the manycatalysts that can be obtained by varying the nature of the Ru complexprecursor, of the diphosphine ligand, of the non-coordinating anions andtheir precursors, and of the non-coordinating or weakly-coordinatingsolvent.

It is to be appreciated that the use of the respective enantiomers ofthe ligands mentioned throughout this specification, for example of(S,S)-(+)-MeDuPHOS or (S)—(R)-JOSIPHOS, makes it possible to obtain thecorresponding enantiomers of compounds of formula (I) and (VI) mentionedabove.

In the examples hereafter, reference to a “glovebox” means a gloveboxunder Ar or nitrogen and the oxygen content of which is under 10 ppm.

EXAMPLE 1 Preparation of [Ru((R,R)-Me-DuPHOS)(H)(COT)](BF₄)

In a glovebox, there were charged into a 50 ml flask 260.7 mg (0.816mmole) of [(COD)Ru(methylallyl)₂] (origin: Acros Organics) and 10.8 mlof methylacetate. A separate 10 ml vial was charged with 250 mg (0.816mmole) of (R,R)-(−)-Me-DuPHOS (origin: STREM Chemicals), 5 ml of CH₂Cl₂and 137 μl of 81% HBF₄.etherate (0.816 mmole of HBF₄). The contents ofthis 10 ml vial were then poured into the stirred mixture contained inthe 50 ml flask and this mixture was further stirred during 12 hours. Ayellow precipitate was collected by filtration (180 mg, 0.299 mmole,yield: 37%), consisting of [Ru((R,R)-Me-DuPHOS)(H)(COT)]⁺BF₄ ⁻ which wasextensively analyzed by spectroscopy. The structure of this crystallineproduct was unambiguously established by spectroscopic analysis. Thedata obtained were the following (¹H and ¹³C NMR established relative totrimethylsilane ; CI=Chemical Ionisation)

¹H NMR(CD₂Cl₂) δ7.58(m, 4H); 6.57(t, J=8.4 Hz, 1H); 6.30(dd, J₁=6.4 Hz,J₂=8.9 Hz, 1H); 5.62(m, 2H); 5.37(q, J=8.4 Hz, 1H); 5.26(t, J=7.9 Hz,1H); 2.71(m, 2H); 2.55-2.15(m, 5H); 1.33(dd, J₁=6.9 Hz, J₂=17.2 Hz, 3H);1.30(m, 1H); 1.13(dd, J₁=6.9 Hz, J₂=17.2 Hz, 3H); 0.93(dd, J₁=6.9 Hz,J₂=17.2 Hz, 3H); 0.70(dd, J₁=6.9 Hz, J₂=17.2 Hz, 3H); −9.94(t, J=29 Hz,1H).

¹³C(¹H) NMR (CD₂Cl₂) δ141.2(m, C), 141.0(m, C), 132.0(d, J_(pc)=14 Hz,CH), 131.5(d, J_(pc)=14 Hz, CH), 131.3(s, CH), 131.0(s, CH), 102.3(s,CH), 101.2(s, CH), 99.2(s, CH), 96.2(s, CH), 94.3(s, CH), 94.3(s, CH),44.5(d, J_(pc)=38 Hz, CH), 44.4(d, J_(pc)=14 Hz, CH), 40.9(d, J_(pc)=32Hz, CH), 40.1(d, J_(pc)=24 Hz, CH), 37.5(s, CH₂), 37.4(s, CH₂), 36.4(s,CH₂), 35.9(s, CH₂), 34.8(s, CH₂), 32.0(s, CH₂), 18.3(s, CH₃), 16.2(d,J_(pc)=6.0 Hz, CH₃), 14.4(s, CH₃), 12.6(s, CH₃);

¹⁹F NMR (CD₂Cl₂) δ10.5 (relative to C₆F₆);

³¹P NMR (CD₂Cl₂) δ87.5 (d, J_(pp)=20.0 Hz), 84.9 (d, J_(pp)=20.0 Hz)(relative to 85% aqueous H₃PO₄);

MS (CI) 515, 339, 287, 231, 209, 193, 180.

The identity of this compound was also ascertained by mass spectrometry,¹H, ¹³C, ¹⁹F, ³¹P NMR spectroscopy, DEPT and ¹H—¹H, ¹H—¹³C correlations.The mass spectrum gives a molecular ion for the cationic portion of thiscomplex at 515 m/e. The ¹⁹F NMR spectrum displays a single resonance fora BF₄ ⁻ moiety indicating the existence of one species. The ³¹P NMRspectrum displays two doublets consistent with one species containingone DuPHOS ligand with inequivalent phosphorous atoms. The ¹H NMRspectrum clearly indicates the presence of a hydride bound to ruthenium,coupled to two phosphorous atoms at −9.94 ppm. Further, there are sixresonances for the CH protons on the cyclooctatriene ligand (which wasalso supported by a ¹H—¹³C correlation). ¹³C (¹H) and DEPT experimentsare also consistent with this structure. There are six resonances forthe cyclooctatriene ligand between 103 and 94 ppm indicating the alkenylnature of this ligand. The methylene groups on the COT ligand wereassigned and are at 35.9 and 32.0 ppm. Further, all remaining ¹³Cresonances are consistent with a single DuPHOS ligand attached toruthenium.

Finally, the structure of the precatalyst mentioned above was alsoconfirmed by X-ray analysis.

The concentration of the commercial HBF₄.etherate in HBF₄ could becarefully monitored before its use, according to the following method.

In a glovebox, a 10 ml glass vial was charged with 20.0 mg (0.050 mmole)of (Ph)₂PCH₂CH₂P(Ph₂) (origin: STREM Chemicals) and 500 μl of CH₂Cl₂. Tothis solution there were added 500 μl of an approximately 0.1 M solutionof HBF₄.etherate/CH₂Cl₂. The solution was placed in a NMR tube, sealedand placed in a NMR probe at −70° C. A ³¹P-proton coupled spectrum wascollected and integrated. By comparing the integral of free(Ph)₂PCH₂CH₂P(PH₂) with the resonances of the protonated diphosphine atrue value for the titre of the HBF₄.etherate/CH₂Cl₂ was obtained.

The title compound was also obtained using [Ru(COD)(COT)] as thestarting ruthenium complex.

EXAMPLE 2 Hydrogenation of methyl3-oxo-2-pentyl-1-cyclopentene-1-acetate

In a glovebox, into a 10 ml glass vial were placed 15.5 mg (0.0485mmole) of [(COD)Ru(methylallyl)₂], 14.9 mg (0.0485 mmole) of(R,R)-Me-DuPHOS and 250 μl of methyl3-oxo-2-pentyl-1-cyclopentene-1-acetate (1.08 mmole). To this suspensionwas added 0.630 ml of a 0.081 M solution of titrated HBF₄.etherate(0.049 mmole) in CH₂Cl₂ with stirring. This concentrated solution wasstirred for 1.5 hours, after which 21.5 g (95.9 mmole) of methyl3-oxo-2-pentyl-1-cyclopentene-1-acetate and 11.5 ml of CH₂Cl₂ wereadded. The resulting yellow solution was placed in a 75 ml autoclave,purged with hydrogen and pressurized to 90 bar of hydrogen. After 8hours, the solution was exposed to air and passed through a column ofsilica gel to separate the catalyst. This gave a 99% yield of thedesired Hedione® product with the following ratios of isomers:cis/trans=98/2; (+)-cis/(−)-cis=82.4/17.6, 64.8% ee.

As prepared above, the catalyst of the invention was present in thereaction medium in 0.05 molar % relative to methyl3-oxo-2-pentyl-1-cyclopentene-1-acetate.

A similar procedure, but adding methyl3-oxo-2-pentyl-1-cyclopentene-1-acetate neat, provided a 99% yield ofthe desired Hedione® product with the following ratios of isomers:cis/trans=98/2; (+)-cis/(−)-cis=83.4/16.6, 66.8% ee.

EXAMPLE 3 Hydrogenation of methyl3-oxo-2-pentyl-1-cyclopentene-1-acetate Using the Catalyst Described inExample 1

In a glovebox, into a 10 ml glass vial were placed 15.0 mg (0.0250mmole) of [((R,R)-Me-Duphos)Ru(H)(cyclooctatriene)]BF₄, 5.62 ml ofCH₂Cl₂ and 11.23 g (50.0 mmole) of methyl3-oxo-2-pentyl-1-cyclopentene-1-acetate. The resulting yellow solutionwas placed in a 75 ml autoclave, purged with hydrogen and pressurized to90 bar of hydrogen. After 6 hours, the solution was exposed to air andpassed through a column of silica gel to separate the catalyst. Thisgave a 99% yield of the desired Hedione® product with the followingratios of isomers: cis/trans=98/2; (+)-cis/(−)-cis=82.3/17.7, 64.6% ee.

Using in the above-described process 7.5 mg of catalyst (0.0125 mmole)provided a final product with the same characteristics as above, in 98%yield, after 33 h of reaction.

Comparative Example 1 Hydrogenation of methyl3-oxo-2-pentyl-1-cyclopentene-1-acetate

Proceeding in a similar manner to that described in Example 2, but inthe presence of a catalyst prepared according to the process describedin WO 97/18894, i.e. using equimolar amounts of[(COD)Ru(2-methylallyl)₂] and diphosphine ligand (see table below),HBF₄.etherate in an amount of 2 molar equivalents per mole of[(COD)Ru(2-methylallyl)₂], in dichloromethane or a mixture of the latterwith other solvents (see table), ethyl 3-oxo-2-pentyl-1-cyclopentene-1-acetate was hydrogenated under a variety of conditions as detailed inthe table below, to provide Hedione® in the form of a variety ofproducts as cited in the table. The molar concentration of the substratein the hydrogenation medium was always approximately the same to avoiddilution effects.

TABLE I Molar % of H₂ Substrate cis/ (+)-cis/ Acid catalyst relativepressure Reaction conversion trans (−)-cis Ligand Hydrogenation solventto substrate (10⁶ Pa) time h % ratio ratio (R,R)-Me-DuPHOS CH₂Cl₂ CH₂Cl₂2 9 0.5 99 97:3 80:20 (R,R)-Me-DuPHOS CH₂Cl₂ CH₂Cl₂ 1 9 1.5 99 98:280:20 (R,R)-Me-DuPHOS CH₂Cl₂ CH₂Cl₂ 0.5 9 20 99 97:3 80:20(R,R)-Me-DuPHOS CH₂Cl₂ CH₂Cl₂ 0.3 5 70 99 99:1 84:16 (R)-(S)-JOSIPHOShexane CH₂Cl₂ 0.2 3.5 20 99 98:2 93:7  (R)-(S)-JOSIPHOS hexane CH₂Cl₂0.1 4 18 98  72:28 90:10 (R)-(S)-JOSIPHOS MTBE* CH₂Cl₂ 0.1 4 20 98 96:489:11 (R)-(S)-JOSIPHOS isopropyl CH₂Cl₂ 0.1 4 18 98 97:3 89:11 ether(R)-(S)-JOSIPHOS cyclohexane CH₂Cl₂ 0.2 3.5 20 96 98:2 93:7 (R)-(S)-JOSIPHOS heptane CH₂Cl₂ 0.1 4 18 97  80:20 90:10 *methyltert-butyl ether

It appears clearly from this table that far longer reaction times areneeded with the method described in WO 97/18894 to obtain fullconversion of the substrate, when the catalyst containing (R,R)-MeDuPHOSis used in a molar concentration below 0.3%, whereas with thecorresponding catalysts of the instant invention the conversion can becomplete in 6 h even when the catalyst is used at 0.05 molar % relativeto the substrate.

Comparative Example 2 Hydrogenation of methyl2,6,6-trimethyl-1-cyclohexene-1-carboxylate

Proceeding as described in WO 97/18894 and in comparative Example 1, theabove substrate was hydrogenated at a pressure close to 100 bar (10⁷ Pa)and at room temperature, using a catalyst which comprised a variety ofligands, as indicated in the table hereafter. In all the trials, 2 molarequivalents of HBF₄.etherate were used per mole of[(COD)Ru(methylallyl)₂] and the catalysts thus obtained were employed at2 molar % concentration with respect to the substrate. The conversionrates, and the isomer characteristics of the methyl(1S,2S)-2,2,6-trimethyl-1-cyclohexane-carboxylate obtained are indicatedin Table 2 hereafter:

TABLE II Reaction Substrate Enantiomeric time conversion Cis/transexcess in Ligand h % ratio (1S,2S)-isomer % (S)-TolBINAP 24 96 99:1 84(R)-TolBINAP 21 96 99:1 85 (−)-MeDuPHOS 21 98 99:1 58 (S)-BINAP 24 7199:1 85

EXAMPLE 4 Hydrogenation of methyl3-oxo-2-pentyl-1-cyclopentene-1-acetate

To a cooled solution of [Ru(COD)(COT)] (30.1 mg, 0.095 mmole) in CH₂Cl₂(5.0 ml) there was added dropwise, under stirring, a diethyl ethersolution (54% weight) of HBF₄ (12.0 μl, 0.087 mml). (R)—(S)-JOSIPHOS(56.4 mg, 0.095 mmole) in CH₂Cl₂ (5.0 ml) was then added and thesolution was allowed to stir for 6 h and then allowed to warm up to roomtemperature. Methyl 3-oxo-2-pentyl-1-cyclopentene-1-acetate was thenadded (catalyst relative to substrate: 0.05%) in methyl tert-butyl ether(v/v=1:1) and the hydrogenation carried out under the usual conditions(90 bar). After 8.5 h there was obtained the desired product with aratio cis/trans=99/1 and (+)-cis/(−)cis=88/12.

What is claimed is:
 1. A ruthenium (II) catalyst comprising the reactionproduct of an appropriate Ru complex, a chelating diphosphine and anacid comprising a non-coordinating anion, said Ru complex and chelatingdiphosphine being present in equimolar amounts, the reaction occurringin a non-coordinating or weakly coordinating medium and under anoxygen-free atmosphere, and the acid comprising a non-coordinating anionbeing used in an amount of about 1 molar equivalent per mole of the Rucomplex.
 2. Catalyst according to claim 1, consisting essentially ofsaid reaction product.
 3. Catalyst according to claim 1, wherein thechelating diphosphine is a chiral diphosphine ligand.
 4. Catalystaccording to claim 3, wherein the Ru complex is selected from the groupof Ru compounds of the formula [(diene)Ru(allyl)₂] or[bis(pentadienyl)Ru].
 5. Catalyst according to claim 3, wherein the Rucomplex is [(COD)Ru(2-methylallyl)₂] or [Ru(COD)(COT)].
 6. Catalystaccording to claim 1, wherein the chelating diphosphine is selected fromthe group consisting of the chiral ligands known under the abbreviationsof Me-DuPHOS, Et-DuPHOS, BINAP, TolBINAP, SKEWPHOS and JOSIPHOS. 7.Catalyst according to claim 6, wherein the chelating diphosphine ligandis selected from the group of chiral diphosphines known under theabbreviations of Me-DuPHOS, SKEWPHOS and JOSIPHOS.
 8. Catalyst accordingto claim 7, wherein the ligand is (R,R)-(−)-MeDuPHOS, (R)—(S)-JOSIPHOSor (R)—(S)—CF₃-JOSIPHOS.
 9. Catalyst according to claim 8, wherein theligand is (R,R)-(−)-MeDuPHOS or (R)—(S)-JOSIPHOS.
 10. Catalyst accordingto claim 1, wherein the non-coordinating anion is a conjugate base of anacid of formula H-Anion, wherein Anion is selected from the groupconsisting of BF₄ ⁻, B[3,5-(CF₃)₂C₆H₄]₄ ⁻, PF₆ ⁻, SbF₆ ⁻, and AsF₆ ⁻.11. Catalyst according to claim 10, wherein the non-coordinating anionis F₄ ³¹ .
 12. Catalyst according to claim 11, wherein the BF₄ ⁻ is inthe form of HBF₄-etherate.
 13. Catalyst according to claim 1, whereinthe weakly coordinating medium is a solvent selected from the groupconsisting of dichloromethane, dichloroethane, ethyl pivalate, methylacetate, ethyl acetate, isopropyl acetate, acetone, 2-butanone,3-pentanone, hexane, heptane, cyclohexane, cycloheptane, methyltert-butyl ether and mixtures thereof.
 14. A process of hydrogenating asubstrate of formula (III) by adding hydrogen across a double bond ofthe substrate in one of the positions indicated by the dotted lines,which addition is catalyzed by the catalyst of claim 1 in a

non-coordinating or weakly coordinating medium and wherein a) n=0 and Zrepresents hydrogen, a C₁ to C₄ linear or branched alkyl radical or anOR¹ group, wherein R¹ stands for a linear or branched lower alkylradical; or b) n=1, X represents a CH₂ group and Z stands for an OR¹group wherein R¹ has the meaning cited in a); or c) n=1, X represents anoxygen atom and Z represents a C₁ to C₄ linear or branched alkylradical, or X represents an NR⁵ group, wherein R⁵ stands for a loweralkyl radical, and Z represents a linear or branched C₁ to C₄ alkylradical; and wherein R² represents hydrogen or a saturated orunsaturated, linear or branched C₁ to C₈ radical derived from ahydrocarbon; R³ and R⁴ are taken separately and each represents hydrogenor a saturated or unsaturated, linear or branched C₁ to C₈ radicalderived from a hydrocarbon, or are taken together to form afive-membered or six-membered ring which also contains the carbon atomsof the ethylenic bond.
 15. The process according to claim 14, whereinthe solvent is selected from the group consisting of dichloromethane,dichloroethane, ethyl pivalate, methyl acetate, ethyl acetate, isopropylacetate, acetone, 2-butanone, 3-pentanone, hexane, heptane, cyclohexane,cycloheptane, methyl tert-butyl ether and mixtures thereof.
 16. Theprocess according to claim 15, wherein the solvent comprisesdichloromethane and the compound of formula (III).
 17. A process ofhydrogenating a substrate of formula (IV)

by adding hydrogen across a double bond of the substrate in one of thepositions indicated by the dotted lines, which addition is catalyzed bythe catalyst of claim 1 in a non-coordinating or weakly coordinatingmedium and wherein: a) n=0 and Z represents a OR¹ group, wherein R¹stands for a C₁ to C₄ linear or branched alkyl radical; or b) n=1, and Zrepresents a C₁ to C₄ linear or branched alkyl radical; and wherein R²is a saturated or unsaturated, linear or branched, C₁ to C₈ hydrocarbonradical and R⁶, R⁷ and R⁸ represent each hydrogen or a lower alkaylradical.
 18. The process according to claim 17, wherein the substrate isa compound of formula (IV) in which n=0 and Z represents a OR¹ group, R¹representing a methyl or ethyl group, R² is methyl and R⁶, R⁷, R⁸ areidentical or different and represent each hydrogen or a methyl group.19. A process of hydrogenating a substrate of formula (II)

by adding hydrogen across the carbon-carbon double bond of thesubstrate, which addition is catalyzed by the catalyst of claim 1 in anon-coordinating or weakly coordinating medium, in which formula R¹ is alinear of branched alkyl radical from C₁ to C₄ and R² is a saturated orunsaturated, linear or branched, C₁ to C₈ hydrocarbon radical.
 20. Theprocess according to claim 19, wherein the substrate is methyl3-oxo-2-pentyl-1-cyclopentene-1-acetate.
 21. The process according toclaim 19, wherein the non-coordinating or weakly coordinating mediumconsists of methyl 3-oxo-2-pentyl-1-cyclopentene-1-acetate.
 22. Theprocess according to claim 19, wherein the Ru complex is[(COD)Ru(2-methylallyl)₂] or [Ru(COD)(COT)], the chelating diphosphineis (R,R)-(−)-Me-DuPHOS, the acid is HBF₄.etherate and thenon-coordinating or weakly coordinating medium comprises dichloromethaneand/or methyl 3-oxo-2-pentyl-1-cyclopentene-1-acetate.
 23. The processaccording to claim 19, wherein the Ru complex is [Ru(COD)(COT)], thechelating diphosphine is (R)—(S)-JOSIPHOS, the acid is HBF₄.etherate andthe non-coordinating or weakly coordinating medium comprises methyltert-butyl ether and/or methyl 3-oxo-2-pentyl-1-cyclopentene-1-acetate.24. The process according to claim 19, wherein the solvent is selectedfrom the group consisting of dichloromethane, dichloroethane, ethylpivalate, methyl acetate, ethyl acetate, isopropyl acetate, acetone,2-butanone, 3-pentanone, hexane, heptane, cyclohexane, cycloheptane,methyl tert-butyl ether and mixtures thereof.
 25. A ruthenium (II)catalyst of formula (V) [Ru(P*−P*)(H)(trien)]⁺Anion⁻  (V) wherein P*−P*represents a chelating chiral diphosphine, Anion represents anon-coordinating anion and “trien” stands for cyclohepta-1,3,5-trien orcycloocta-1,3,5-trien.
 26. Catalyst according to claim 25, wherein thechelating chiral diphosphine is (R,R)-(−)-Me-DuPHOS or (R)—(S)-JOSIPHOS.27. Catalyst according to claim 25, wherein Anion is BF₄ ⁻, PF₆ ⁻, SbF₆⁻, or AsF₆ ⁻.
 28. Process for the preparation of a ruthenium (II)catalyst in which an appropriate Ru complex and a chealatingdiphosphine, present in equimolar amounts, and an acid comprising anon-coordinating anion are reacted under an oxygen-free atmosphere andin a non-coordinating or weakly coordinating medium, wherein thenon-coordinating anion is used in an amount of about 1 molar equivalentper mole of the Ru complex.
 29. The process according to claim 28,wherein the catalyst is prepared in the presence of a non-coordinatingor weakly coordinating medium comprising a hydrogenatable substrate ofthe formula

in which R¹ is a linear or branched alkyl radical from C₁ to C₄ and R²is a saturated or unsaturated, linear or branched, C₁ to C₈ hydrocarbonradical, or of the formula

having a hydrogenatable double bond in one of the positions indicated bythe dotted lines and wherein: a) n=0 and Z represents a OR¹ group,wherein R¹ stands for a C₁ to C₄ linear or branched alkyl radical; or b)n=1, and Z represents a C₁ to C₄ linear or branched alkyl radical; andwherein R² is a saturated or unsaturated, linear of branched, C₁ to C₈hydrocarbon radical and R⁶, R⁷ and R⁸ represent each hydrogen or a loweralkyl radical.
 30. A ruthenium (II) catalyst obtained by a process whichcomprises putting into contact an appropriate Ru complex, a chelatingdiphosphine and an acid comprising a non-coordinating anion, said Rucomplex and chelating diphosphine being present in equimolar amounts,the contact occuring in a non-coordinating or weakly coordinating mediumand under an oxygen-free atmosphere, wherein the acid comprising anon-coordinating anion is used in an amount of about 1 molar equivalentper mole of the Ru complex.
 31. A ruthenium (II) ester hydrogenationcatalyst comprising the reaction product of an appropriate Ru complex, achelating diphosphine and an acid comprising a non-coordinating anion,said Ru complex and chelating diphosphine being present in equimolaramounts, the reaction occurring in a non-coordinating or weaklycoordinating medium and under an oxygen-free atmosphere, wherein theacid comprising a non-coordinating anion is used in an amount of about 1molar equivalent per mole of the Ru complex.